Real Time CSF Flow Measurement System &amp; Method

ABSTRACT

A system for measuring quantitative CSF flow in shunt tubing implanted under the skin. The system includes an array of thermo-sensors clustered in three sections, cooling device, placed on the skin surface and an associated data acquisition and analysis device. Two sensor sections are placed over the shunt on the skin and measure real time temperature responses related to CSF movement. One array placed adjacent the cooling device collects data on thermal properties of skin including skin thermal conductivity, specific heat, diffusivity, perfusion, and thermal inertia. The method involves assessing thermal properties of skin and measuring CSF flow in shunt tubing. The method is useful for shunt patency assessment, CSF valve adjustment procedures and CSF flow measurements related to CSF over drainage. Alternatively, only one section of sensors need be used when determining relative CSF flow, without the need to determine thermal skin properties and by applying the cooling device continuously.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation application which claims the benefit under 35U.S.C. §120 of application Ser. No. 13/698,689 filed on Dec. 27, 2012which in turn is a national phase application and claims the benefitunder 35 U.S.C. §371 of International Application No. PCT/US2011/038317filed on May 27, 2011 which in turn claims the benefit under 35 U.S.C.§119(e) of Provisional Application Ser. No. 61/396,436 filed on May 28,2010, all of which are entitled REAL TIME CSF FLOW MEASUREMENT SYSTEMAND METHOD and all of whose entire disclosures are incorporated byreference herein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with government support under R43NS074486 andR44NS074486 awarded by the National Institutes of Health. The governmenthas certain rights in the invention.

BACKGROUND OF THE INVENTION

1. Field of Invention

This present invention generally relates to cerebrospinal fluid (CSF)shunts and, more particular, to a device and method for testing for thepresence, absence and/or rate of flow in the shunt tubing implantedunder the skin.

2. Description of Related Art

Approximately 69,000 people are diagnosed with hydrocephalus each yearin the United States [1]. There are approximately 300,000 shuntedhydrocephalus patients in the US [3][4]. The one-year shunt failure rateof shunts is approximately 40% [15, 16], and the mean period to failureis typically only 5-10 years [17]. Obstruction of the ventricularcatheter is overwhelmingly the greatest cause [4, 15, 18-20]. Sincecatheter replacement requires surgery, a need for shunt revision must bereasonably established. Hydrocephalus is a condition of CSFdysregulation, resulting in accumulation of fluid in the brainventricles. It can lead to neurodegeneration and death if untreated. Itis most commonly treated by diverting CSF to the peritoneal cavity bymeans of a permanent prosthetic shunt.

The usual clinical manifestations of shunt failure (headaches, vomiting)are non-specific, making shunt obstruction difficult to differentiatefrom less serious illnesses, particularly in pediatric patients in whomthree false alarms are seen for every true malfunction [4]. Physicalexamination, including pumping of the shunt reservoir, is unreliable[21]. CT (computed tomography) remains the gold standard [4, 9], howeveradvanced imaging techniques produce static results, are expensive andcannot be used to investigate every headache, and result in repeatedradiological exposures of patients (often children). Current dynamicmeasures of shunt flow generate only bivariate analyses of “flow” or “noflow” (FIG. 7). New technologies under development are complex(ultrasound tracking of bubbles), lacking in precision (FLIR) or requireimplantation (implanted thermal flow technologies) and have not reachedthe clinic.

Thus, there remains a need for a device capable of determining absoluteCSF flow rate which has two clinically important applications that arenot possible with imaging or bivariate flow measures: (1) prediction ofimpending catastrophic shunt failure, i.e., monitoring shunt flow inroutine examinations enables early recognition of a diminishing flowrate trend in a failing shunt and pre-emption of catastrophic failure;and (2) monitoring and adjusting shunt valve settings to accommodateindividual needs for CSF drainage. The degree of impairment in drainingCSF varies from hydrocephalic patient to patient. Adjustable shuntvalves avoid under drainage and over drainage by the shunt. While thesettings for these valves in each patient must currently be determinedempirically over a number of weeks, the invention of the presentapplication provides guidance to neurosurgeons and quicker stabilizationof CSF homeostasis. In addition to these clinical applications, theshunt flow detection device developed here provides an importantresearch tool for CSF flow behavior in hydrocephalus patients.

All references cited herein are incorporated herein by reference intheir entireties.

BRIEF SUMMARY OF THE INVENTION

An apparatus for determining cerebrospinal fluid (CSF) flow rate in animplanted CSF shunt is disclosed. The apparatus comprises: a pad that isplaced against the skin of a patient over the location of the CSF shuntwherein the said pad comprises: a first plurality of temperature sensors(e.g., thermistors) that are aligned in a transverse direction withrespect to the CSF shunt and wherein one of the first plurality oftemperature sensors is aligned with the CSF shunt; and a secondplurality of temperature sensors that are aligned in a transversedirection with respect to the CSF shunt, downstream of the firstplurality of temperature sensors, and wherein one of the secondplurality of temperature sensors is aligned with the CSF shunt; and athird plurality of temperature sensors associated with a temperaturesource (e.g., a Peltier device, an ice cube, etc.) that positioned overthe CSF shunt whenever the pad is placed against the skin; and a sensorprocessing device that is electrically coupled to the pad for receivingtemperature data from each of the plurality of temperature sensors, andwherein the sensor processing device uses the temperature data to removethe effects of skin depth of CSF implantation, skin thermal conductivityand skin thermal diffusivity from temperature data collected by thefirst, second and third pluralities of temperature sensors, and fordetermining a flow rate of the CSF through the CSF shunt when atemperature source is applied to the pad.

A method for determining cerebrospinal fluid (CSF) flow rate in animplanted CSF shunt is disclosed. The method comprises: applying a firstplurality of temperature sensors against the skin over the location ofthe CSF shunt and wherein only one of the first plurality of temperaturesensors (e.g., thermistors) is aligned with the CSF shunt; applying asecond plurality of temperature sensors against the skin over thelocation of the CSF shunt, downstream of the first plurality oftemperature sensors, and wherein only one of the second plurality oftemperature sensors is aligned with the CSF shunt; associating a thirdplurality of temperature sensors with a temperature source (e.g., aPeltier device, an ice cube, etc.), wherein the temperature source beingapplied against the skin is aligned with the CSF shunt; collectingtemperature data from the first, second and third plurality oftemperature sensors after a predetermined period of time has elapsed;removing the effects of skin depth of CSF implantation, skin thermalconductivity and skin thermal diffusivity; and determining a flow rateof the CSF through the CSF shunt from the temperature data.

An apparatus for determining intracranial pressure (ICP) of patienthaving an implanted cerebrospinal fluid (CSF) shunt with an adjustableshunt valve (e.g., a Codman Hakim programmable valve) is disclosed. Theapparatus comprises: a pad comprising a plurality of temperature sensors(e.g., thermistors) and a temperature source, said pad being adaptableto be secured to the skin of the patient over a portion of the implantedCSF, and wherein the plurality of temperature sensors detects themovement of a temperature pulse introduced into the CSF of the CSFshunt; a sensor processing device that is electrically coupled to thepad for receiving temperature data from each of the plurality oftemperature sensors and for displaying a CSF flow or no CSF flowcondition to an operator; and a remote controller for adjusting theadjustable shunt valve; and wherein an operator of the apparatusmonitors the sensor processing device to determine if there is or is notany CSF flow and wherein the operator uses the remote controller tochange an opening valve pressure of the adjustable shunt valve from anexisting valve pressure to a known opening pressure to either initiate aCSF flow that did not previously exist; or to stop an existing CSF flow;and from either of these scenarios determine the ICP based upon theknown opening pressure.

A method for determining intracranial pressure (ICP) of a patient havingan implanted cerebrospinal fluid (CSF) shunt with an adjustable shuntvalve (e.g., a Codman Hakim programmable valve) is disclosed. The methodcomprises: positioning a plurality of temperature sensor arrays (e.g.,thermistors) that can detect the passage of a temperature changeexperienced by the CSF passing in said CSF shunt and a temperaturesource (e.g., a Peltier device, an ice cube, etc.), against the skin ofa patient over the location of the CSF shunt; analyzing temperature datacollected by the plurality of temperature sensors arrays to determine ifthere is any CSF flow in the CSF shunt or not, wherein the flow-no flowstatus is visible to a user; adjusting the adjustable shunt valve tochange an opening valve pressure from an existing valve pressure to aknown opening valve pressure to either initiate a CSF flow that did notpreviously exist; or to stop an existing CSF flow; and determining theICP based upon the known opening valve pressure.

An apparatus for controlling cerebrospinal fluid (CSF) flow in animplanted CSF shunt having an adjustable shunt valve (e.g., a CodmanHakim programmable valve) is disclosed. The apparatus comprises: a padcomprising a plurality of temperature sensors (e.g., thermistors) and atemperature source, wherein the pad is adaptable to be secured to theskin of the patient over a portion of the implanted CSF, and wherein theplurality of temperature sensors detects the movement of a temperaturepulse introduced into the CSF of the CSF shunt; a sensor processingdevice that is electrically coupled to the pad for receiving temperaturedata from each of the plurality of temperature sensors and fordisplaying a CSF flow or no CSF flow condition to an operator; and aremote controller for adjusting the adjustable shunt valve; and whereinan operator of the apparatus monitors the sensor processing device todetermine a flow rate of the CSF in the CSF shunt and then uses theremote controller to change an opening valve pressure of the adjustableshunt valve to achieve a desired CSF flow rate.

A method for controlling cerebrospinal fluid (CSF) flow in an implantedCSF shunt having an adjustable shunt valve (e.g., a Codman Hakimprogrammable valve) is disclosed. The method comprises: positioning aplurality of temperature sensor arrays (e.g., thermistors) that candetect the passage of a temperature change experienced by the CSFpassing in the CSF shunt and a temperature source, against the skin of apatient over the location of the CSF shunt; analyzing temperature datacollected by the plurality of temperature sensors arrays to inform auser of a CSF flow rate; and adjusting the adjustable shunt valve by theuser to change an opening valve pressure of the adjustable shunt valveto change the CSF flow rate to a desired CSF flow rate.

An apparatus for determining cerebrospinal fluid (CSF) flow rate in animplanted CSF shunt is disclosed. The apparatus comprises: a pad that isplaced against the skin of a patient over the location of the CSF shunt,and wherein the pad comprises: a first plurality of temperature sensors(e.g., thermistors) that are aligned in a transverse direction withrespect to the CSF shunt and wherein one of the first plurality oftemperature sensors is aligned with the CSF shunt; and at least onetemperature sensor associated with a temperature source (e.g., a Peltierdevice) that is positioned over the CSF shunt whenever the pad is placedagainst the skin and wherein the temperature source is appliedcontinuously (e.g., 5 minutes or more) against the skin; and a sensorprocessing device that is electrically coupled to the pad for receivingtemperature data from each of said temperature sensors during thecontinuous application of the temperature source, and for determining aflow rate of the CSF through the CSF shunt from the temperature data.

A method for determining cerebrospinal fluid (CSF) flow rate in animplanted CSF shunt is disclosed. The method comprises: applying a firstplurality of temperature sensors against the skin over the location ofthe CSF shunt and wherein only one of the first plurality of temperaturesensors is aligned with the CSF shunt; associating at least onetemperature sensor with a temperature source (e.g., a Peltier device);activating the temperature source against the skin continuously andaligned with the CSF shunt, wherein the activating the temperaturesource comprises applying a temperature to the skin continuously (e.g.,5 minutes or more) that is different from a skin temperature; collectingtemperature data from the temperature sensors during the continuousactivation of the temperature source; and determining a flow rate of theCSF through the CSF shunt from the temperature data.

BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS

The invention will be described in conjunction with the followingdrawings in which like reference numerals designate like elements andwherein:

FIG. 1 is an illustration of a two sensor array configuration for CSFshunt flow measurements of the present invention and wherein the CSFshunt is implanted under the skin;

FIG. 2 is a top view of isotherms on the skin surface and temperaturesensor distribution;

FIG. 3 is an illustration of the present invention depicting the sensorwith a cooling-heating device positioned over the implanted CSF shunt;

FIG. 3A is a top view of a configuration similar to FIG. 3 but showingthe temperature sensors associated with the cooling-heating device in aslightly different orientation;

FIG. 4 is an illustration of ventriculoperitoneal shunt placement;

FIG. 5 is an illustration of isotherms after ice cube removal from theskin wherein the left panel shows isotropic heat transfer in animal(viz., pig) skin and the right panel shows isotropic heat transfer inhuman skin. It should be noted that there is no shunt underneath the twoskins and the isotherms show no “triangular” shape as is shown in FIG.2;

FIG. 6 ShuntCheck temperature dip vs flow rate for subcutaneous shunt ina porcine model;

FIG. 7 is an illustration of ShuntCheck procedure (ice application) andthe resulting temperature graph with corresponding bivariate output (inthis case: flow confirmed);

FIG. 8 is a graph showing T′ vs depth of implantation (skin thicknessoverlaying the shunt) using four flow rates for each skin thickness;

FIG. 9 is an illustration of the possible embodiment of the coolingapparatus and single array sensor of the present invention wherein panelA is a cross-section of the cooling apparatus which is a plastic-coveredice cube, and panel B is a bottom view of the sensing patch;

FIG. 10 includes a lower graph that shows true flow rates changing intime and an upper graph showing Peltier variable flow, temperature vs.time; and

FIG. 11 shows a partial cross-sectional view of a patient' skull andclavicle showing the implanted shunt and adjustable shunt valve andwherein the ShuntCheck device is disposed on the skin surface at theclavicle.

DETAILED DESCRIPTION OF THE INVENTION

The present invention 20 overcomes the deficiencies of the prior art byproviding a system of thermosensors strategically placed on the skinsurface and a cooling system. In particular, the present invention 20provides a CSF real time, thermal flow measurement method and systemwhich are capable of compensating for changing thermal properties of theskin and which are also capable of compensating for skin thickness(e.g., depth of shunt tubing implantation). The present invention 20also provides a method of CSF real time, thermal flow measurement systemwhich is based on three sets (arrays) of sensors and a cooling device.In addition, the present invention 20 also provides a method of shuntvalve adjustment based on information provided by the CSF flow measuringsystem. Moreover, the present invention 20 provides a method of ICPassessment based on information provided by the CSF flow measuringsystem and settings of the adjustable shunt valve.

This invention 20 (see FIGS. 1 and 3) is the first rapid andnon-invasive method for determining CSF flow rate through shunts inhydrocephalus patients. This invention 20 is an improvement uponShuntCheck technology. The term “ShuntCheck” is a term used by theAssignee, namely, NeuroDx Development LLC, to identify the configurationof its apparatus that detects CSF shunt flow using a sensor patch 320applied to the skin 301 of the patient and disposed over the implantedCSF shunt 310 and an associated CSF analyzer 400 that collects the datafrom the sensors on the sensor patch and either analyzes this datadirectly to provide CSF flow results or transmits such data to anotherdevice for CSF flow analysis.

The existing ShuntCheck FDA 510k cleared device (see U.S. applicationSer. No. 12/936,162 filed Oct. 1, 2010, entitled “Cerebrospinal FluidEvaluation System Having Thermal Flow and Flow Rate Measurement PadUsing a Plurality of Control Sensors” is incorporated by reference inits entirety herein) is the starting platform for developing a novelsystem capable of determining absolute flow rate of fluid through asubcutaneous shunt. The platform consists of a single-use disposablethermosensor and a PDA based handheld device 400 (FIG. 3) that analyzestemperature-time data to provide a bivariate “flow” or “no-flow” result(FIG. 7). Ice applied on skin over shunt upstream causes surfacetemperature change of skin downstream, thereby indicating CSF flowinside. The thermosensor is an adhesive patch with temperature sensors(thermistors, by way of example only, the thermistors may comprise theMA100 Catheter Assembly which has a thermal response time in still waterof 2.0 seconds. Another exemplary thermistor is the GE NTC thermistor)that is placed on the skin where the shunt crosses the clavicle. Ice isplaced on the skin over the shunt catheter and “upstream” of thethermistors to cool the CSF inside. The change in temperature ismeasured by the thermosensor as cooled fluid flows beneath itsthermistors. In this first generation device, the presence or absence offluid flow is interpreted by a threshold magnitude (≧0.2° C.) change intemperature over time. The basis for believing that the platform iscapable of determining the flow rate of the shunt fluid is that dataobtained in an animal model indicate that the magnitude of temperaturechange detected by ShuntCheck is correlated to the magnitude of theshunt flow rate (FIG. 6). The limitation of the method for determiningabsolute flow rate, which is solved in current invention, is that skinsurface temperatures are related not only to flow rate of fluid in theshunt, but also to other factors which vary among patients:

TABLE 1 Factors which can affect skin temperature readings Factorssolution Shunt depth in skin Method for determining and compensating fordepth Skin thermal conductivity, Method for measuring & specific heat &density compensating for thermal properties

Preliminary data indicate that the components of the thermal dilutiondata that are dependent upon skin thickness and thermal propertyvariability can be identified and removed from the data analysis,leaving only results that are dependent upon fluid flow rate. Thisenables the development of “quantitative ShuntCheck”, able to measureabsolute flow rates (not relative flow rates) reliably from test to testand person to person.

In addition, it has been determined that providing low level (safe forthe skin tissue) constant cooling by a Peltier device (skin cooled downto about 20 Celsius) allows for long term real time measurements of CSFflow (see FIG. 10). The lower plot of FIG. 10 shows true flow rates inthe shunt changing in time and the upper plot of FIG. 10 showscorresponding temperature output from a quantitative ShuntCheck device.It is clear that the thermal output corresponds closely to the simulatedCSF flow in the shunt. Thus this method is suitable for real timemonitoring of CSF flow.

This mode of operation is applicable for long term monitoring ofpatients, without necessity of repeated ice or other coolantapplication, by maintaining constant cold input to the system via thePeltier device and measuring CSF flow.

This feature combined with skin thickness compensation, and skin thermalproperties assessment provides for long term, real time accurate CSFflow measurements.

Preliminary Data

There is a significant correlation between skin surface temperaturechange and shunt flow rate.

Thermal dilution data collected using the first generation ShuntCheck inan animal model indicate that the magnitude of temperature changedetected by the thermosensors is highly correlated to flow rate (FIG.6). A young porcine model was chosen as model because its skin is mostsimilar to humans [22-27]. 7 Day old piglets (n=5) were implanted with asubcutaneous shunt through which warmed fluid (37° C.) was flowed atknown rates using a volumetric pump. As flow rate was increased over thephysiological range, the magnitude of the temperature change recorded byShuntCheck increased linearly. The temperature change is calculated as adifference between the middle sensor 123 (FIG. 1) temperature and theaverage of two external sensors temperatures 122, 124 which arepositioned against the skin 100 over the implanted shunt 110, which isat a skin depth, d (130). The same is true with regard to the secondarray of sensors 120, 121 and 125. This suggests that thermal dilutiontechnology, which is now used only to determine the presence or absenceof flow through the shunt, could be used to obtain absolute flow ratesof fluid through a subcutaneous shunt if inter-patient variability infactors other than flow rate that contribute to thermal dilution, suchas skin thickness, thermal conductivity and diffusivity, can bemeasured.

FIG. 2 provides a plan view of the sensor patch application site showingthe temperature isotherms on the skin surface in relation to theposition of the temperature sensors of FIG. 1. If the temperature sourceused upstream of the temperature sensors in FIG. 2 were, e.g., an icecube, then isotherm T_(A) would be the coldest detected temperature,isotherm T_(B) would be slightly warmer and T_(C) would be the warmest.Thus, references 215, 210 and 211 correspond to the positions of thetemperature sensors 124, 123 and 122 respectively. Similarly, references222, 213 and 212 correspond to the positions of the temperature sensors125, 121 and 120, respectively.

T Prime (T′) is Indicator for Skin Thickness Regardless of Flow Rate

A bench-top apparatus was created and validated to simulate our animalmodel—a heated body core (35 deg C.), covered by a silicon phantom skinwith an implanted shunt (embedded in silicone) attached to a syringepump so ShuntCheck tests could be run with known flow rates. Skinthickness of 3, 4, 6 and 7 mm were tested. As expected, we found thatindividual temperature changes detected on the “skin” overlying theshunt were influenced by the depth of the shunt. We next investigatedvarious analysis techniques to identify the depth-dependent componentsof temperature measurement over the shunt. Two thermosensor arrays 321and 322 (each consisting of three thermistors 330, 331, 332; and 333,334 335, respectively, in a straight line perpendicular to the shunt soone sensor is over the shunt and two are adjacent for controls) wereplaced with a distance between them of 7 mm A series of 16 ShuntChecktests were run using four flow rates (5, 10, 15 & 20 ml/h) for each ofthe four skin thicknesses. We found that one analysis feature (which isreferred to as T′) was highly dependent upon skin thickness (FIG. 8),and less so upon flow rate. Therefore, when the thermal properties oftissue are known, the depth of shunt implantation can be determined Oncethe depth of implantation is determined from T′, an empirical formulafor that particular skin thickness could be used to determine the flowrate. It should be noted that data points for several flows overlap. T′is a temperature gradient between two sensor arrays divided by the timeneeded to achieve maximum temperature dip on the first sensor array(inset) and wherein error bars represent 1 std error. This formuladescribes the relationship shown in FIG. 6 but calibrated to theparticular skin thickness Importantly, these data demonstrate that thedepth of a shunt can be determined from surface temperature data, andeliminated from the analysis to (in part) enable absolute flow rates tobe determined from thermal dilution data.

T′ was calculated as ratio between the maximum temperature drop on thesecond array 321 and time needed for this maximum to occur. Thetemperature drop on the second array was calculated as temperaturemeasured by sensor 331 minus the average of temperatures measured bysensors 330 and 332.

A Method for Determining the Thermal Properties of Skin for Each Test

Variability in skin conductivity (k), and diffusivity (α) are the finalfactors which must be compensated for in order to accurately measureflow rate of CSF in a shunt. To achieve this, we must find the effectivek and α for each subject at the time of each quantitative flow rate testbecause they differ within and between subjects.

${{\nabla^{2}T} + \frac{q}{k} + {\frac{1}{k}W_{b}{C_{b}\left( {T_{b} - T} \right)}}} = {\frac{1}{\alpha}\frac{\partial T}{\partial T}}$${{\nabla^{2}T} + \frac{q^{\prime}}{k_{eff}} - \frac{q_{ice}}{k_{eff}}} = {\frac{1}{\alpha_{eff}}\frac{\partial T}{\partial t}}$

The Penne's bio-heat equation is shown above along with a reducedversion that removes but accounts for perfusion via effectiveconductivity. The latter is commonly used in skin heat transferproblems, and requires k_(eff) (effective skin conductivity) and α_(eff)(effective diffusivity) in order to solve for temperatures. Since thoseparameters are not known, the inverse problem must be solved wheretemperatures are used to determine them during each test. EachShuntCheck test consistently removes a specific amount of energy fromthe system (skin and tissue) by cooling the skin surface with ice. Theice cube is a well defined cold source, isolated from the environment bya thermally insulating cup (see FIG. 9) and exposed only to skin, andwith a known volume, specific heat and density. In particular, as shownin FIG. 9, panel A is a cross section of the cooling apparatus, aplastic covered ice cube in the thermal insulator. Tissue comes incontact with the ice cube at the bottom exposed side of the cube. Byplacing a thermistor inside this ice cube one can estimate q drainedfrom tissue. Panel B of FIG. 9 shows the bottom view of the sensingpatch with one array of thermal sensors measuring downstream temperaturechanges on the skin surface after cooling, this design is capable ofmeasuring flow when d, k, c, and p are fixed. Adding one more arraydownstream allows for compensating for skin thickness, while addinganother side array permits the measurement of thermal properties oftissue. By measuring the ice cube temperature one can estimate theamount of energy being absorbed by the ice cube. Under steady stateconditions (which occurs in unshunted skin at about t=150 s; see FIG.7), the temperature drop measured on the skin surface at a fixeddistance will be proportional to skin conductivity and the amount ofenergy drained from tissue. When a thermosensor is placed on unshuntedskin about 10 mm from where ice is applied for 60 sec, the temperaturevs time cooling curve will reach a minimum, indicating a near steadystate condition before it is re-warmed by autoregulation. Its shape issimilar to the graph shown in FIG. 7 but with a shallower and flatterbottom since there would be no shunt or flow. The steady state heattransfer equation can then be solved for k_(eff):

${\frac{q}{\frac{T}{x}}{Const}} = k_{eff}$

where q is heat absorbed by the ice cube over a predefined period oftime;

dT/dx is the temperature gradient registered by the sensor array at apoint of steady state after 60 sec cooling; and

Const is a constant specific to setup geometry which can be obtained bycalibration with a material of known conductivity, k.

Effective diffusivity, α_(eff), can then be obtained by adding the timedomain gradient measurement according the equation:

${\frac{\partial^{2}T}{\partial x^{2}} + \frac{\partial^{2}T}{\partial y^{2B}} + \frac{q}{k_{eff}}} = {\frac{1}{\alpha_{eff}}\frac{\partial T}{\partial t}}$

These methods enable all significant parameters needed for an accurateflow rate measurement to be determined for each ShuntCheck test. Oncethese values are known, the correct temperature vs time characteristicfor the specific conductivity and diffusivity can be used to determinethe flow rate, which is accurate because it accounts for the factorsthat vary in patients.

In the preferred embodiment 20 there are three sensor arrays 321, 322,323 as shown in FIG. 3. One sensor array 323 (comprising temperaturesensors 336, 337 and 338, and also referred to as the “side array”)collects data on cooling device 340 temperature, skin-cooling deviceinterface 337, and skin 301 temperature (far from the shunt tubing 310).The second sensor array 322 (comprising temperature sensors 333, 334 and335, also referred to as the “proximal array”) and the third sensorarray 321 (comprising temperature sensors 330, 331 and 332, alsoreferred to as the “distal array”) overlay the shunt tubing (FIG. 1,sensors 120, 121, 122, 123, 124). Those two arrays are responsible formeasuring thermal changes related to CSF flow. The sensor arrays areattached to the skin surface 301 by an adhesive patch 320. In yetanother embodiment they are attached by vacuum or adhesive paste (notshown). It should be understood that the second and third sensor arrayshave their respective temperature sensors positioned on the surface ofthe sensor patch 320 that is placed against the skin 301. The same istrue for sensors 337 and 338.

The preferred embodiment 20 comprises also a cooling-heating device 340placed next to the sensor arrays 322, 320 and 323. The cooling-heatingdevice 340 can be electronically powered and controlled (e.g. Peltierdevice). In another preferred embodiment it utilizes cold/warm mediasuch as water, other fluid, ice (FIG. 9), dry ice, or cooling/warmingspray. The cooling device cools down or heats up the skin surface 301,tissue 300 beneath the skin surface and section of the shunt tubing 310(implanted at a skin depth d, or 311) with CSF fluid. Thecooling-heating device is placed upstream or downstream of the second322 and third 321 sensor arrays. The cooling device 340 is attached tothe skin 301 via adhesive patch 320. In yet another embodiment it isattached by vacuum or adhesive paste not shown). The sensor array 323,used to calculate skin properties, is placed partially on the skin inlocation not overlaying the shunt tubing.

The downstream positioning of the cooling-heating device can best beunderstood considering whether there is CSF flow or no CSF flow. Forexample, in a situation where there is no CSF flow and thecooling-heating device (e.g., an ice cube) is positioned downstream ofthe distal array 321 (but not too far), cold temperature migrates in alldirections from the position of the ice cube and part of that “coldmigration” is detected by the distal array 321 and then the proximalarray 322. Alternatively, if there is CSF flow and the ice cube is againplaced downstream of the distal array 321 (but not too far), thetemperature of the warm CSF flow warms the ice cube and this “warmingmigration” is detected by the distal array 321 and then the proximalarray 322. Thus, locating the cooling-heating device downstream of thetemperature sensor arrays is still an effective method of detecting CSFflow.

The system comprises also a reader-controller unit 400 (e.g., a CSFanalyzer comprising a processor with I/O) which collects data from allsensors (via a cable 340 or via a wireless configuration, not shown).The reader-controller unit 400 comprises a display 402 and keypad orother input mechanism 404. The reader-controller unit 400 can alsocontrol cooling-heating device 340 by increasing, decreasing orstabilizing 1) temperature or 2) heat generated or absorbed by thecooling device. The reader-controller unit 400 is capable of recordingtime stamps triggered by an operator or other external device. The timestamps indicate on the thermal data stream a precise point in time whenthe time stamp was triggered by an operator or an external machine. Thereader-controller unit 400 also controls the activation of thetemperature source 340 (e.g., Peltier device), as mentioned previously,either for heating or for cooling.

FIG. 3A is an illustration showing metrological configuration of thesensor patch necessary to accomplish skin depth and thermal propertiescompensation with real time multipoint measurement. In particular, FIG.3A is a top view of a configuration similar to FIG. 3 but showing thetemperature sensors associated with the cooling-heating device in aslightly different orientation. In particular, the sensors 337 and 338are shown as sensors 337′ and 338′ aligned along an x-axis that isparallel to the CSF shunt and they are displaced away from the CSF shuntalong a perpendicular axis, i.e., y-axis. As can also be seen from FIG.3A, each of the sensors in the arrays 322 and 321 are aligned in adirection parallel to the CSF shunt. Furthermore, in each array the twoouter or “control” sensors (i.e., 333/335 in array 322 and 332/330 inarray 321) are displaced symmetrically (“s”) along the y-axis from theCSF shunt.

The method(s) for actually calculating the CSF flow rate is discussedbelow and the terms T1, T2 and T3 refer to the temperature (T1) sensedby the central temperature sensors (e.g., 334 and 331) located over theshunt, the temperature (T2) sensed by the “right” control sensors (e.g.,333 and 330) and the temperature (T3) sensed by the “left” controlsensors (e.g., 335 and 332).

It should be understood that the temperature source 340 could be eithera cooling device or a heating device.

Calculating Flow Rate

In general, this method requires a lookup table(s) which has to be builtexperimentally for each model. The lookup table facilitates findingconstants A, B, C, etc., used in model equations (see below). Then, theequation is used to calculate the flow rate (F).

1. Determine thermal conductivity k_(eff) (as described previously)2. Determine thermal diffusivity ∀_(eff) (as described previously)3. Determine shunt depth (T′ parameter)The temperature source 340 (e.g., cooling device) has to be activatedfor a short period of time (e.g. 60 sec) and then turned off. Duringthis period (during cooling and several minutes after) the temperatureson the two arrays 321 and 322 are measured.4. Calculate the flow rate. The following calculations provide severaloptions for calculating absolute flow rate:Option 1: Calculate flow using a linear approximation (this solutionworks best for low flow rates of e.g., 0-20 ml/h)With ∀, k and T′ known, go to the look up table and find correspondingconstants A, B;Calculate flow (F) using A and B and the linear equation:

F=A*[T1−(T2+T3)/2]+B,

using T1, T2 and T3 from any array 321 or 322.Option 2: Calculate flow using a polynomial approximation (this solutionworks best for extended range or flows of e.g., 0-60 ml/h)With ∀, k and T′ known, go to the look up table and find correspondingconstants A, B, C, D, and E and calculate the flow (F) using:

F=A*[T1−(T2+T3)/2]̂4+B*[T1−(T2+T3)/2]̂3+C*[T1−(T2+T3)/2]̂2+D*[T1−(T2+T3)/2]+E,

using T1, T2 and T3 from any array 321 or 322.

Option 3A: Exponential Approximation

With ∀, k and T′ known, go to the look up table and find correspondingconstants A, B and C using the following exponential approximation:

F=Â[(B*(T1−(T2+T3)/2))]+C,

using T1, T2 and T3(e.g. 333, 334, 335, FIG. 3) from any array 321 or 322. Temperaturesensors have to belong to the same array (similar to the traditionalShuntCheck configuration).

Option 3B: Exponential Approximation

With ∀, k and T′ known, go to the look up table and A′, B′ and C′ andcalculate flow from:

F=A′̂[(B′*(θ)]+C′)

where θ is the temperature difference between any pair of temperaturesensors (e.g., thermistors) placed over the shunt tubing (e.g., 334 and331 for T1) and so, in this case, the temperature sensors don't have tobelong to the same array.

It should be understood that the reader-control unit 400 comprises amicroprocessor or microcontroller that can employ these variouscalculations on the received temperature sensors' data or it cantransmit the temperature sensors' data remotely (by cable or wirelessly)where the flow calculation is conducted and outputted (visibly fordisplay or audibly).

It should be understood that the present invention can determinerelative CSF flow (e.g., no flow, increased flow, decreased flow, etc.)or absolute CSF flow (“z” ml/h). As discussed previously, to determineabsolute CSF flow, the parameters of skin thickness T′,k_(eff)(effective skin conductivity) and α_(eff) (effective diffusivity)must first be determined and then the temperature data from the varioustemperature sensor arrays analyzed.

To determine relative CSF flow, it is not necessary to first determinethese three parameters; instead, the temperature data from thetemperature sensor arrays can be analyzed and a relative flow can bedetermined from the equations involving T1, T2 and T3 discussed above.As mentioned previously, U.S. application Ser. No. 12/936,162 filed Oct.1, 2010, entitled “Cerebrospinal Fluid Evaluation System Having ThermalFlow and Flow Rate Measurement Pad Using a Plurality of Control Sensors(whose entire disclosure is incorporated by reference herein) disclosesa similar process. However, unlike Ser. No. 12/936,162, the presentinvention 20 employs the controllable temperature source 340 thatapplies a given temperature for continuous period of time, rather than ashort or abrupt pulse of temperature as disclosed in Ser. No.12/936,162. For example, where an ice cube is applied in Ser. No.12/936,162 for a short period of time (e.g., 60 seconds) and thenremoved, in the present invention 20, the temperature source 340 (e.g.,a Peltier device) applies a substantially smaller temperature step tothe skin of the patient and for a continuous period of time (e.g., 1hour, 5 hours, 10 hours, 24 hours, etc.). Thus, the term “continuous” asused in this Specification implies a substantial period of time that isfor more than 5 minutes. Moreover, in Ser. No. 12/936,162, thetemperature sensors collect data once the temperature source (e.g., theice cube) is removed whereas in the present invention, the temperaturesensor arrays are continuously collecting temperature data while thetemperature source 340 is active. To accomplish this, the temperaturesource 340 applies a temperature magnitude that can be detected by thetemperature sensor arrays but which is not uncomfortable to the patientsince the temperature source 340 (e.g., the Peltier device) is applyingthis temperature for a continuous period of time. So, for example, thePeltier device 340 can be programmed, or controlled by thereader-controller unit 400, to apply a temperature to the skin that is7°-14° C. lower than the skin temperature. Such a temperature differenceis sufficient for the temperature sensors to detect the “cold” bolus inthe CSF flow in the CSF shunt but yet which is not uncomfortable to thepatient during the testing. Furthermore, in determining such relativeflow, the use of a second array of temperature sensors is not required;hence, relative flow can be determined with either sensor array 322 or321. In addition, this relative flow determination can also be achievedvia the use of only one temperature sensor associated with thetemperature source 340; for example, a temperature sensor (e.g., 336)placed on the temperature source 340 or a temperature sensor (e.g., 337)placed between it and the skin would be sufficient to determine relativeflow.

Determining Intracranial Pressure (ICP) or Setting CSF Flow UsingShuntCheck

The system can also be used along with adjustable (programmable) valvessuch as “Codman Hakim programmable valve” in order to assess patient'sICP. As shown in FIG. 11 by way of example only, an adjustable CSF shuntvalve 800 forms part of the implanted CSF shunt 310 and the valve 800 istypically located behind the ear 14 of the patient. Thus, this valve 800is located well upstream of where the sensor patch 320 is positioned(e.g., typically over the clavicle 15 of the patient (as also shown inFIG. 7) during use. Details of two such methods are described below:

The method of ICP assessment is claimed. Because the “opening pressure”of the adjustable shunt valve is a known parameter (e.g., 12 cmH₂O),this method can be utilized if there is no natural CSF flow in theshunt. The operator takes following steps 1) continuously observes flowmeasured by the ShuntCheck device; and 2) simultaneously decreasesopening pressure of the CSF shunt valve; the shunt valve openingpressure can be controlled by an operator using a remote control 802(e.g., via magnetic coupling), as shown in FIG. 11. The moment whenShuntCheck detects CSF flow, it is correlated with opening pressure ofthe valve 800, i.e., the opening pressure of the adjustable shunt valve800 coincides with first CSF flow detection and thus this identifies theICP. The operator of the remote control 802 is provided with a display,dial or other output mechanism (e.g., audible clicking, etc.) thatindicates the current setting of the opening pressure of the adjustableshunt valve 800.

The method is claimed of using the system, when there is CSF flow in theshunt, in such a way that the operator 1) continuously observes CSF flowmeasured by the ShuntCheck device and 2) simultaneously the operatorincreases the opening pressure of the adjustable shunt valve (again,using the remote controller). The moment when ShuntCheck observes thatthere is no longer any CSF flow, again, this correlates with openingpressure of the valve. The opening pressure of the adjustable shuntvalve coincides with the first “no-flow” detection and is then equal toICP.

Similarly, this ShuntCheck device and adjustable shunt valveconfiguration can be used to obtain a desired CSF flow. In particular,the method is claimed of using this configuration in the followingmanner. If there is no CSF flow in the CSF shunt, the physician may makea determination based on the patient's age, weight, size, and/or otherparameters, that a certain CSF flow should be present. The physicianwould monitor the ShuntCheck device as he/she used the remote control802 to decrease the opening pressure of the valve 800 until the desiredCSF flow is displayed on the ShuntCheck device at which time thephysician would stop adjusting the valve. Conversely, if the patientwere suffering from “overdrainage” (i.e., too much CSF flow wherebynegative pressure is generated in the cranium which could result inhemorrhaging), the physician would monitor the ShuntCheck device ashe/she used the remote control 802 to increase the opening pressure ofthe valve 800 until the desired CSF flow is displayed on the ShuntCheckdevice at which time the physician would stop adjusting the valve 800.

While the invention has been described in detail and with reference tospecific examples thereof, it will be apparent to one skilled in the artthat various changes and modifications can be made therein withoutdeparting from the spirit and scope thereof.

REFERENCES CITED

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What is claimed is:
 1. An apparatus for determining cerebrospinal fluid(CSF) flow rate in an implanted CSF shunt, said apparatus comprising: apad that is configured to be placed against the skin of a patient overthe location of the CSF shunt, said pad comprising: a first plurality oftemperature sensors that are configured to be aligned in a transversedirection with respect to said CSF shunt and wherein one of said firstplurality of temperature sensors is configured to be aligned with theCSF shunt; and at least one temperature sensor associated with atemperature source that is positioned over the CSF shunt whenever saidpad is placed against the skin and wherein said temperature source isapplied continuously against the skin; and a sensor processing devicethat is electrically coupled to said pad for receiving temperature datafrom each of said temperature sensors during said continuous applicationof said temperature source, and for determining a flow rate of said CSFthrough said CSF shunt from said temperature data.
 2. The apparatus ofclaim 1 wherein said sensor processing device controls the activation ofsaid temperature source.
 3. The apparatus of claim 1 wherein saidtemperature source is a Peltier device.
 4. The apparatus of claim 3wherein said Peltier device maintains a temperature that differs from askin temperature.
 5. The apparatus of claim 4 wherein said temperaturediffers from said skin temperature by approximately 7°-14° C.
 6. Theapparatus of claim 3 wherein said continuous application of saidtemperature source is at least 5 minutes.
 7. The apparatus of claim 1further comprising a second plurality of temperature sensors that areconfigured to be aligned in a transverse direction with respect to saidCSF shunt, downstream of said first plurality of temperature sensors,and wherein one of said second plurality of temperature sensors isconfigured to be aligned with the CSF shunt.
 8. The apparatus of claim 1wherein said at least one temperature sensor associated with atemperature source comprises a temperature sensor that is positioned onsaid temperature source or is configured to be positioned between saidtemperature source and the skin surface.
 9. The apparatus of claim 7wherein said at least one temperature sensor associated with atemperature source further comprises at least one other temperaturesensor disposed adjacent said temperature source.
 10. A method fordetermining cerebrospinal fluid (CSF) flow rate in an implanted CSFshunt, said method comprising: applying a first plurality of temperaturesensors against the skin over the location of the CSF shunt and whereinonly one of said first plurality of temperature sensors is aligned withthe CSF shunt; associating at least one temperature sensor with atemperature source; activating said temperature source against the skincontinuously and aligned with the CSF shunt, said activating saidtemperature source comprises applying a temperature to the skincontinuously that is different from a skin temperature; collectingtemperature data from said temperature sensors during said continuousactivation of said temperature source; and determining a flow rate ofthe CSF through the CSF shunt from said temperature data.
 11. The methodof claim 10 wherein said temperature source is a Peltier device.
 12. Themethod of claim 11 wherein said Peltier device maintains a temperaturethat differs from a skin temperature.
 13. The method of claim 12 whereinsaid temperature differs from said skin temperature by approximately7°-14° C.
 14. The method of claim 10 wherein said continuous activationof said temperature source is at least 5 minutes.
 15. The method ofclaim 10 wherein said step of applying a first plurality of temperaturesensors comprises applying a second plurality of temperature sensorsagainst the skin over the location of the CSF shunt, downstream of saidfirst plurality of temperature sensors, and wherein only one of saidsecond plurality of temperature sensors is aligned with the CSF shunt.16. The method of claim 10 wherein said step of associating at least onetemperature sensor with a temperature source comprises positioning atemperature sensor on said temperature source or positioning saidtemperature sensor between said temperature source and the skin surface.17. The method of claim 16 wherein said step of positioning atemperature sensor on said temperature or positioning said temperaturesensor between said temperature sensor and the skin surface furthercomprises positioning at least one other temperature sensor adjacentsaid temperature source.